Clinical and epidemiological characteristics of septic arthritis of the hip, 2006 to 2012, a seven-year review

OBJECTIVE:

To epidemiologically characterize the population treated at our orthopedic clinic with a diagnosis of septic arthritic of the hip between 2006 and 2012.

METHODS:

Fifteen patients diagnosed with septic arthritis of the hip between 2006 and 2012 were retrospectively evaluated. The patients'' clinical and epidemiological characteristics were surveyed; a sensitivity profile relating to the microorganisms that caused the infections and the complications relating to the patients'' treatment and evolution were identified.

RESULTS:

Septic arthritis was more common among males. Most diagnoses were made through positive synovial fluid cultures, after joint drainage was performed using the Smith-Petersen route. Among the comorbidities found, the most prevalent were systemic arterial hypertension, diabetes mellitus, and human immunodeficiency virus. The pathological joint conditions diagnosed prior to joint infection were osteoarthrosis and developmental dysplasia of the hip. The infectious agent most frequently isolated was Staphylococcus aureus. From the clinical and laboratory data investigated, 53.33% of the cases presented with fever, and all except one patient presented with increased measures in inflammation tests. Gram staining was positive in only 26.66% of the synovial fluid samples analyzed. Six patients presented with joint complications after treatment was administered.

CONCLUSION:

S. aureus is the most common pathogen in acute infections of the hip in our setting. Factors such as clinical comorbidities are associated with septic arthritis of the hip. Because of the relatively small number of patients, given that this is a condition of low prevalence, there was no statistically significant correlation in relation to worse prognosis for the disease.     

Reduced Abundance of Nitrate-Reducing Bacteria in the Oral Microbiota of Women with Future Preeclampsia

The oral microbiota can contribute to the regulation of blood pressure by increasing the availability of nitric oxide through the reduction of nitrate to nitrite, which can be converted into nitric oxide in the stomach and then enter the circulation. It is unclear if the composition of the oral microbiota is different between women who do and do not develop preeclampsia. This study aimed to compare the composition of the buccal microbiota just prior to the development of symptoms at 36 weeks gestation in 12 women who developed late-onset preeclampsia and 24 matched women who remained normotensive throughout pregnancy by 16S rRNA gene amplicon sequencing. The abundance of the nitrate-reducing Veillonella spp V. parvula and V. dispar and a subunit of nitrate reductase narH was compared using real-time PCR. The abundance of bacteria was correlated with maternal blood pressure and dietary intake of nitrate-containing vegetables. The results showed that the abundance of nitrate-reducing bacteria including Veillonella, specifically V. parvula, and Prevotella was reduced in women who developed preeclampsia. Veillonella but not Prevotella abundance was negatively correlated with maternal blood pressure. The dietary intake of nitrate-containing vegetables did not differ between the groups and was not correlated with the abundance of Veillonella. There was no difference in the abundance of the nitrate reductase subunit narH between the groups. These results suggest that the abundance of nitrate-reducing bacteria is reduced in the oral microbiota of women who later develop preeclampsia, indicating a potential pathway for prevention.     

Is Secretory Activation Delayed in Women with Type Two Diabetes? A Pilot Study

(1) Background: Breastfeeding duration may be reduced in women with type 2 diabetes. Delayed secretory activation (SA) is associated with poorer breastfeeding outcomes; however, no prior studies have examined SA in women with type 2 diabetes. This pilot study aimed to assess SA in women with type 2 diabetes by assessing breastmilk constituents. Secondary aims were to assess breastfeeding rates postpartum, and contributory factors. (2) Methods: A prospective cohort of pregnant women with type 2 diabetes (n = 18) and two control groups with age- and parity-matched nondiabetic pregnant women (body mass index (BMI)) matched (n = 18) or normal-range BMI (n = 18)) were recruited. Breastmilk constituents (citrate, lactose, protein, and fat) were measured twice daily for 5 days postpartum and compared between groups. Associations between peripartum variables, breastmilk constituents, and breastfeeding at 4 months postpartum were explored. (3) Results: Women with type 2 diabetes had a slower increase in breastmilk citrate concentration postpartum, indicative of delayed SA, compared to both control groups. Higher predelivery insulin doses in women with type 2 diabetes were associated with increasing time to SA. Both women with type 2 diabetes and BMI-matched controls were less likely to fully breastfeed at 4 months, compared with normal-BMI controls. (4) Conclusion: SA is delayed in women with type 2 diabetes when compared to BMI-matched and normal-BMI women. Women with type 2 diabetes are less likely to fully breastfeed, at hospital discharge and by 4 months postpartum, compared to women with normal-BMI.     

IGF-1R pathway activation as putative biomarker for linsitinib therapy to revert tamoxifen resistance in ER-positive breast cancer

Preclinical studies indicate that activated IGF-1R can drive endocrine resistance in ER-positive (ER+) breast cancer, but its clinical relevance is unknown. We studied the effect of IGF-1R signaling on tamoxifen benefit in patients and we searched for approaches to overcome IGF-1R-mediated tamoxifen failure in cell lines. Primary tumor blocks from postmenopausal ER+ breast cancer patients randomized between adjuvant tamoxifen versus nil were recollected. Immunohistochemistry for IGF-1R, p-IGF-1R/InsR, p-ERα(Ser118), p-ERα(Ser167) and PI3K/MAPK pathway proteins was performed. Multivariate Cox models were employed to assess tamoxifen efficacy. The association between p-IGF-1R/InsR and PI3K/MAPK pathway activation in MCF-7 and T47D cells was analyzed with Western blots. Cell proliferation experiments were performed under various growth-stimulating and -inhibiting conditions. Patients with ER+, IGF-1R-positive breast cancer without p-IGF-1R/InsR staining (n = 242) had tamoxifen benefit (HR 0.41, p = 0.0038), while the results for p-IGF-1R/InsR-positive patients (n = 125) were not significant (HR 0.95, p = 0.3). High p-ERα(Ser118) or p-ERα(Ser167) expression was associated with less tamoxifen benefit. In MCF-7 cells, IGF-1R stimulation increased phosphorylation of PI3K/MAPK proteins and ERα(Ser167) regardless of IGF-1R overexpression. This could be abrogated by the dual IGF-1R/InsR inhibitor linsitinib, but not by the IGF-IR-selective antibody 1H7. In MCF-7 and T47D cells, stimulation of the IGF-1R/InsR pathway resulted in cell proliferation regardless of tamoxifen. Abrogation of cell growth was regained by addition of linsitinib. In conclusion, p-IGF-1R/InsR positivity in ER+ breast cancer is associated with reduced benefit from adjuvant tamoxifen in postmenopausal patients. In cell lines, stimulation rather than overexpression of IGF-1R is driving tamoxifen resistance to be abrogated by linsitinib.     

Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer

MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.     

The photobiology of the human circadian clock

In modern society, the widespread use of artificial light at night disrupts the suprachiasmatic nucleus (SCN), which serves as our central circadian clock. Existing models describe excitatory responses of the SCN to primarily blue light, but direct measures in humans are absent. The combination of state-of-the-art neuroimaging techniques and custom-made MRI compatible light-emitting diode devices allowed to directly measure the light response of the SCN. In contrast to the general expectation, we found that blood oxygen level–dependent (BOLD) functional MRI signals in the SCN were suppressed by light. The suppressions were observed not only in response to narrowband blue light (λ_max: 470 nm) but remarkably, also in response to green (λ_max: 515 nm) and orange (λ_max: 590 nm), but not to violet light (λ_max: 405 nm). The broadband sensitivity of the SCN implies that strategies on light exposure should be revised: enhancement of light levels during daytime is possible with wavelengths other than blue, while during nighttime, all colors are potentially disruptive.

Due to the Earth’s rotation around its axis, many organisms developed an internal clock to anticipate the predictable changes in the environment that occur every 24 h, including the daily light–dark cycle. In mammals, this clock is located in the suprachiasmatic nucleus (SCN), located in the hypothalamus directly above the optic chiasm (1, 2). The SCN receives information from the retina regarding ambient light levels via intrinsically photosensitive retinal ganglion cells (ipRGCs), thus synchronizing its internal clock to the external light–dark cycle. ipRGCs contain the photopigment melanopsin, which is maximally sensitive to blue light, with a peak response to 480-nm light (3, 4). In addition, ipRGCs also receive input from rod cells and cone cells (5–7). The three cone cell subtypes in the human retina respond maximally to 420-nm, 534-nm, and 563-nm light, while rod cells respond maximally to 498-nm light (8). In rodents, input from cone cells renders the SCN sensitive to a broad spectrum of wavelengths (9), while rod cells mediate the SCN’s sensitivity to low-intensity light (10, 11). Recently, these findings in rodents were proposed to translate to humans (12), suggesting that the human clock is not only sensitive to blue light, but may also be sensitive to other colors.In humans, circadian responses to light are generally measured indirectly (e.g., by measuring melatonin levels or 24-h behavioral rhythms). These indirect measures revealed that circadian responses to light in humans are most sensitive to blue light (13–16); however, green light has also been found to contribute to circadian phase shifting and changes in melatonin to a larger extent than would have been predicted based solely on the melanopsin response, suggesting that rods and/or cones may also provide functional input to the circadian system in humans (17). Despite this indirect evidence suggesting that several colors can affect the human circadian clock, this has never been measured directly due to technical limitations. Thus, current guidelines regarding the use of artificial light are based solely on the clock’s sensitivity to blue light. For example, blue light is usually filtered out in electronic screens during the night (18, 19), and blue-enriched light is used by night shift workers to optimize their body rhythm for achieving maximum performance (20–22).The ability to directly image the human SCN in vivo has been severely limited due to its small size and the relatively low spatial resolution provided by medical imaging devices. Previous functional MRI (fMRI) studies using 3-Tesla (3T) scanners were restricted to recording the “suprachiasmatic area,” which encompasses a large part of the hypothalamus and thus includes many other potentially light-sensitive nuclei (23–25). To overcome this limitation, we used a 7T MRI scanner, which can provide images with sufficiently high spatial resolution to image small brain nuclei (26) such as the SCN. Here, we applied colored light stimuli to healthy volunteers using a custom-designed MRI-compatible light-emitting diode (LED) device designed to stimulate specific photoreceptors while measuring SCN activity using fMRI. Using analytical approaches, we then identified the SCN’s response, the smallest brain nucleus that has so far been imaged. We found that the human SCN responds to a broad range of wavelengths (i.e., blue, green and orange light). Surprisingly, we also found that the blood oxygen level–dependent (BOLD) fMRI signal at the SCN is actually suppressed—not activated—by light.     

The effect of nightshift on emergency registrars' clinical skills

Objective: The effect of nightshift on ED staff performance is of clinical and risk‐management significance. Previous studies have demonstrated deterioration in psychomotor skills but the present study specifically assessed the impact of nightshift on clinical performance. Methods: The ED registrars in a tertiary hospital were enrolled in a prospective observational study and served as their own controls. During nightshift, subjects were presented simulated scenarios and tested with eight clinical questions developed to Fellowship examination standard. Matched scenarios and questions for the same subjects during dayshift served as controls. Two investigators, blinded to subject identity and the setting in which questions were attempted, independently collated answers. Results: Of 22 eligible subjects, all were recruited; four were excluded owing to incomplete data. A correlation of 0.99 was observed between the independent scoring investigators. Of a possible score of 17, the median result for nightshift was 9.5 (interquartile range: 8–11); corresponding value for dayshift was 12 (interquartile range: 10–13); P= 0.047. Conclusion: Nightshift effect on clinical performance is anecdotally well known. The present study quantifies such effects, specifically for the ED setting, and paves the way for focused research. The implications for clinical governance strategies are significant, as the fraternity embraces the mandate to maintain quality emergency care 24 h per day.